i. Collagenous Biological Tissues Used For Prosthetic Grafting
Various tissues of biological origin have heretofore been used as prosthetic grafts for surgical implantation in or attachment to the body of a human being. As used herein, the term "graft" shall refer to any type of tissue or organ used for subsequent implantation or transplantation, including for example, certain cardiovascular tissues (e.g., segments of blood vessels, heart valves, pericardium), integumentary tissues (e.g., skin), tendons, or other tissues which have been harvested from human or other mammalian sources.
Prior to surgical implantation or transplantation of a graft of biological origin, the graft tissue is typically subjected to a chemical tanning or preservation treatment. The preserved tissue is then stored until it is needed for surgical implantation or grafting into the body of a human patient.
Biological tissues of the type used for allergenic or xenogeneic grafting in human beings (e.g., heart valves, pericardium, blood vessel, skin, etc. . . ) typically contain a connective tissue matrix. Such connective tissue matrix acts as the supportive framework for the tissue. The cellular parenchyma of the living tissue is disposed within, and supported by, such connective tissue framework.
Collagen and elastin are two substances which make up the connective tissue framework of most biological tissues. The flexibility or rigidity of biological tissue is determined largely by the relative amounts of collagen and elastin present therewithin and/or the physical structure and configuration of the connective tissue framework.
Collagen is a naturally occurring substance which, on a molecular level, consists of three polypeptide chains intertwined in a coiled helical confirmation. The individual amino acid constituents of each polypeptide chain are connected, by way of carbon bonds, to the adjacent amino acids of a neighboring polypeptide chain. Such amino acid bonding serves to hold the polypeptide chains in the triple helical confirmation of the collagen molecule.
Collagenous biological tissues may be tanned or preserved for subsequent surgical grafting and/or implantation by a chemical "fixing" process wherein the collagen network of the graft tissue is exposed to one or more chemical cross linking agents capable of forming chemical cross linkages between the amine groups of the collagen molecules.
The chemical cross linkages formed by the fixative agent include both "intramolecular" and "intermolecular" cross linkages. Intramolecular cross linkages are formed between the amine groups on neighboring polypeptide chains within a particular collagen molecule, while intermolecular cross linkages are formed between amine groups located on different collagen molecules. In general, it is desirable to accomplish substantially complete intramolecular cross linking of collagen within a biological graft material, with only minimal formation of intermolecular cross linkages within such material. Indeed, a high intramolecular cross link density and low intermolecular cross link density is typically associated with the most desirable preservation and physical properties of the resultant biological graft.